title: Efficient and rapid generation of induced pluripotent stem cells from human keratinocytes.
abstract: The utility of induced pluripotent stem (iPS) cells for investigating the molecular logic of pluripotency and for eventual clinical application is limited by the low efficiency of current methods for reprogramming. Here we show that reprogramming of juvenile human primary keratinocytes by retroviral transduction with OCT4, SOX2, KLF4 and c-MYC is at least 100-fold more efficient and twofold faster compared with reprogramming of human fibroblasts. Keratinocyte-derived iPS (KiPS) cells appear indistinguishable from human embryonic stem cells in colony morphology, growth properties, expression of pluripotency-associated transcription factors and surface markers, global gene expression profiles and differentiation potential in vitro and in vivo. To underscore the efficiency and practicability of this technology, we generated KiPS cells from single adult human hairs. Our findings provide an experimental model for investigating the bases of cellular reprogramming and highlight potential advantages of using keratinocytes to generate patient-specific iPS cells.
authors.affiliation: Center of Regenerative Medicine in Barcelona, Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Trond
authors.initials: T
authors.lastname: Aasen
authors.forename: Angel
authors.initials: A
authors.lastname: Raya
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Barrero
authors.forename: Elena
authors.initials: E
authors.lastname: Garreta
authors.forename: Antonella
authors.initials: A
authors.lastname: Consiglio
authors.forename: Federico
authors.initials: F
authors.lastname: Gonzalez
authors.forename: Rita
authors.initials: R
authors.lastname: Vassena
authors.forename: Josipa
authors.initials: J
authors.lastname: Bilić
authors.forename: Vladimir
authors.initials: V
authors.lastname: Pekarik
authors.forename: Gustavo
authors.initials: G
authors.lastname: Tiscornia
authors.forename: Michael
authors.initials: M
authors.lastname: Edel
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Boué
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Izpisúa Belmonte
mesh_terms: D000328:Adult; D001709:Biotechnology / Q000379:methods; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D065150:Cellular Reprogramming; D002675:Child, Preschool; D006801:Humans; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000235:genetics; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000166:cytology* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012190:Retroviridae / Q000235:genetics; D055748:SOXB1 Transcription Factors / Q000235:genetics; D013997:Time Factors; D014161:Transduction, Genetic
chemical_list: C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; C489427:MYC protein, human; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D016271:Proto-Oncogene Proteins c-myc; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors